Angiogenesis is a phenomenon in which a new vascular network is formed from an existing blood vessel and is observed mainly in a microvessel. Angiogenesis is originally a physiological phenomenon and is essential for blood vessel formation in fetal life, but it is usually observed only at a limited site such as endometrium or follicle or at a limited period such as a wound healing process in adults. However, pathological angiogenesis is observed in a disease such as cancer, rheumatoid arthritis, age-related macular degeneration, diabetic retinopathy, retinopathy of prematurity, retinal vein occlusion, polypoid choroidal angiopathy, diabetic macular edema, psoriasis vulgaris or atherosclerosis, and closely relates to the progress of pathological conditions of these diseases. It is considered that angiogenesis is regulated by balance between its promoting factor and inhibitory factor, and angiogenesis is caused by disruption of the balance (see Molecular Medicine vol. 35, special issue, “Molecular Mechanism of Symptoms and Pathological conditions”, Nakayama Syoten, 73-74 (1998), and Protein, Nucleic Acid and Enzyme, extra number, “The Most Advanced Development of New Drugs”, Kyoritsu Shuppan, 1182-1187 (2000)).
A vascular endothelial growth factor (hereinafter abbreviated as “VEGF”) is a factor which specifically acts on a receptor (Flt-1, KDR/Flk-1 or the like) present on the surface of vascular endothelial cells, thereby to promote proliferation and migration of the vascular endothelial cells, construction of a capillary vessel network due to vasculogenesis, and plays a very important role in incidence of angiogenesis. Accordingly, there have been many reports on attempts to treat a disease associated with angiogenesis by inhibiting VEGF to control the incidence of angiogenesis. Examples of drugs to be used for the treatment include indolin-2-one derivatives (see WO 98/50356), phthalazine derivatives (see WO 98/35958), quinazoline derivatives (see WO 97/30035), anthranilic acid amide derivatives (see WO 00/27819), 2-aminonicotinic acid derivatives (see WO 01/55114), 4-pyridylalkylthio derivatives (see WO 04/078723) and the like.
However, there is no description on cyclic compounds having a quinolylalkylthio group in these Patent publications.
On the other hand, compounds having a chemical structure relatively close to those of cyclic compounds having a quinolylalkylthio group are reported in WO 98/37061 and WO 96/09294. The former relates to arylsulfonamide derivatives and discloses a therapeutic effect on neurodegenerative diseases as its application. Further, the latter relates to substituted heterocyclic compounds and discloses an inhibitory effect on p56lck protein-tyrosine kinase as its application. However, both of these Patent publications disclose only enormous combinations of chemical structures, and do not make specific disclosure of cyclic compounds having a quinolylalkylthio group at all.